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| United States Patent |
5,051,256
|
|
Barnes
|
September 24, 1991
|
Biocidal complex and dressing formed therefrom
Abstract
A novel complex of polypyrrolidone, also known as nylon-4, and iodine is
disclosed. The complex has biocidal properties exhibiting especially the
fungicidal and bactericidal properties of free iodine but not its
irritating and toxic properties. The complex may be formed with
polypyrrolidone having any physical form, e.g. a powder, film, pulp, fiber
or molded article. Bandage material made from nylon-4 fibers and complexed
with iodine is a particularly useful form. Ointments and other
compositions for topical application may also be made.
| Inventors:
|
Barnes; Carl E. (482 Trinity Pass, New Canaan, CT 06840)
|
| Appl. No.:
|
443878 |
| Filed:
|
November 30, 1989 |
| Current U.S. Class: |
424/402; 2/901; 424/78.06; 424/78.07; 424/78.25; 424/400; 424/443; 424/445; 424/446; 525/356; 525/357 |
| Intern'l Class: |
A61K 009/00; A61F 013/00; A61L 015/00 |
| Field of Search: |
424/78,667,670,402,443,446,445,400
|
References Cited
U.S. Patent Documents
| 2638463 | May., 1953 | Ney et al. | 424/78.
|
| 3287222 | Nov., 1966 | Larde et al. | 424/80.
|
| 3674901 | Jul., 1972 | Shepherd et al. | 424/27.
|
| 3751565 | Aug., 1973 | Santorelli | 424/150.
|
| 3764669 | Oct., 1973 | Santorelli | 424/80.
|
| 3890280 | Jun., 1975 | Upadhyaya | 260/78.
|
| 3984341 | Oct., 1976 | Haschke et al. | 424/150.
|
| 4113851 | Sep., 1978 | Leveen et al. | 424/28.
|
Other References
Chem. Abst. 82: 86797(t) (1975)-Kaneniwa et al.
Chem. Abst. 93: 192,048(m) (1980)-Aita et al.
Chem. Abst. 100: 86933(z) (1984)-Barnes et al.
|
Primary Examiner: Waddell; Frederick E.
Assistant Examiner: Weddington; Kevin E.
Attorney, Agent or Firm: Davis Hoxie Faithfull & Hapgood
Parent Case Text
RELATED APPLICATIONS
This is a continuation of copending application(s) Ser. No. 07/155,942
filed on Feb. 16, 1988 now abandoned.
Claims
What is claimed is:
1. A composition having biocidal activity comprising a complex of
polypyrrolidone and iodine.
2. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a bandage material.
3. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a suture.
4. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a finely divided powder.
5. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a film.
6. A composition according to claim 1 wherein the polypyrrolidone is in the
form of fibrils.
7. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a woven fabric.
8. A composition according to claim 1 wherein the polypyrrolidone is in the
form of a non-woven fabric.
9. A composition according to claim 1 in the form of a molded article.
10. A composition according to claim 1 wherein the polypyrrolidone is in
the form of a fiber.
11. The composition of claim 1 in the form of an ointment.
12. The composition of claim 1 in the form of a powder.
13. An antiseptic dressing for direct application to wounds of the bodies
of humans and animals which comprises a complex of polypyrrolidone and
iodine.
14. The method of preparing a complex of polypyrrolidone and iodine which
comprises the steps of contacting the polypyrrolidone with an aqueous
solution of iodine in potassium iodide for a period of time sufficient to
allow the formation of the complex, removing the polypyrrolidone from the
aqueous solution and washing the polypyrrolidone with water to remove the
excess potassium triiodide solution.
15. The method of claim 14 in which the temperature of the aqueous
potassium iodide solution is in the range from 15.degree. C. to 60.degree.
C.
16. The method of preparing a complex of polypyrrolidone and iodine which
comprises contacting polypyrrolidone with iodine vapors.
Description
BACKGROUND OF THE INVENTION
The iodine complex formed by mixing polyvinylpyrrolidone (PVP) and iodine,
first disclosed in U.S. Pat. No. 2,739,922 issued to Herman A. Shelanski,
has established itself as the preferred way of utilizing the desirable
biocidal properties of iodine while avoiding the irritating side effects.
It has become the product of choice especially in surgery where it is used
to coat the skin prior to incision.
PVP is a water soluble polymer and likewise the PVP-iodine complex is water
soluble. There are applications however in which this solubility in water
is undesirable. For example in topical applications the effectiveness of a
water soluble antiseptic is of short duration since it is readily washed
away not only by water but by the exudate from the wound. A water
insoluble complex which slowly releases small amounts of iodine would be
much more permanent and effective.
OBJECTS OF THE INVENTION
It is a primary object of this invention to provide a water insoluble and
therefore more permanent complex of iodine possessing medicinal
properties.
It is another object of this invention to provide a water insoluble complex
of iodine which slowly releases elemental iodine in small but effective
amounts over a long period of time thus prolonging the microbiological
activity while minimizing the irritating side effects.
It is a further object of the invention to provide a novel bandage and
suture material which in itself is the bactericidal and fungicidal agent.
It is a still further object of this invention to provide water insoluble
long lasting antiseptic ointments for topical application.
Other objects will be apparent in the detailed disclosure which follows.
DESCRIPTION OF PREFERRED EMBODIMENTS
It has been found that polypyrrolidone, also known as nylon4, a polymer
having the structure
##STR1##
can be made to form a complex with elemental iodine which is an iodophor,
exhibiting sustained release of iodine. This complex is not soluble in
water, thus making it longer lasting in most applications for human and
veterinary treatment.
It is surprising and unexpected that nylon-4 should form a complex with
iodine since the pyrrolidone ring, which is intact in PVP, is opened and
non-existent in nylon-4 which has instead a polyamide structure.
Nevertheless it has been found that a complex with iodine will form very
easily.
The polypyrrolidone employed to make the iodine complex may be in any
physical form such as a finely divided resin, a pulp (i.e., fibrils), a
molded article, a film (extruded or cast), as well as filaments for use in
sutures, or textile fibers from which a fabric may be made by knitting or
weaving.
The complex is best formed by immersing the nylon-4 article in a solution
of iodine in aqueous potassium iodine, i.e., KI.sub.3. A preferred formula
is:
______________________________________
Potassium iodide 4.0 grams
Iodine 2.0 grams
Water 100 ml
______________________________________
Upon immersion in this solution the white polypyrrolidone article turns to
a dark chocolate-brown color almost immediately and then becomes black.
Upon drying the color becomes somewhat lighter. Immersion times can range
from a few seconds to about five minutes, or longer. Shorter immersion
times will produce a golden yellow color in the dried article while longer
times will give a dark brown color in the dried material. However the
amount of iodine to be complexed is best controlled by the amount of
iodine added to the complexing solution, i.e., its concentration. Up to
about 20% of iodine in the complex can be added. Higher amounts of iodine
will degrade the polymer and should be avoided.
The color of the dried complex is a measure of the amount of iodine present
and may range from a golden yellow to a deep brown. At 20% iodine content
the color is almost black. Complexes having a pale yellow color do not
contain enough iodine to be effective in most applications.
The iodine complex may be formed by other methods such as exposing the
nylon-4 article to iodine vapor or triturating finely ground resin powder
or particles with solid iodine crystals; however immersion in the KI.sub.3
solution is best.
The iodine is rather tightly held in the complex. By way of comparison, if
cotton (another hydrophilic fiber) is immersed in an iodine solution
prepared according to the recipe given above it develops a similar dark
brown color. But the iodine is only loosely held and washes out completely
with tap water within a minute. Likewise silk also develops a dark brown
color but while the iodine does not wash out as readily as it does with
cotton, only a tan color remains indicating but a small amount of iodine
remaining in the fibers. The iodine in the dark brown complex formed with
nylon-4 does not readily wash out with water. Small amounts of iodine are
released however at a rate which is dependent on the temperature. The rate
is very slow at room temperature but at about 100.degree. C. it is quite
rapid. For example, if the complex in the form of a fabric is placed in
boiling water the iodine will be removed completely in a matter of
minutes. Similarly if placed in an oven at 100.degree. C. the iodine will
sublime out of the complex very rapidly leaving a colorless nylon-4
fabric. At 40.degree. C. no appreciable loss of iodine occurs within 24
hours. Samples may be kept for several weeks at room temperature without
appreciable loss of iodine. However, when the complexed material is to be
stored for longer periods of time, such as a year or more, it should be
placed in a container which is impermeable to iodine vapor. Plastic bags
made from a laminate of polyethylene and nylon films manufactured by Mobil
Chemical company are suitable for this purpose.
In order to be effective as an antiseptic or bactericide, a slow release of
iodine must occur, and at body temperature this release takes place at
about the proper rate. For many reasons a bandage should be changed every
24 hours but it should remain effective during this period of time. An
important feature of the nylon-4 iodine complex is that, unlike its
PVP-iodine counterpart, if the bandage or other dressing gets wet, even
from perspiration, the biocidal agent is not washed away.
Another embodiment of the invention is as a biocidal suture. In this
application the polypyrrolidone resin is melt extruded at temperatures of
about 290.degree. C. under high pressure generated by the screw of the
extruder. Care must be taken to dry the resin to not more than about 0.06%
moisture content before extruding and the resin must be kept under dry
nitrogen in the hopper feeding the extruder to prevent further moisture
pick-up.
The molten resin is forced through a spinnerette consisting of a single
hole to form a monofilament or multiple holes to form a multifilament
suture. As is well known to those skilled in the art, the size of the hole
and the amount of draw determine the diameter of the filament or filaments
as well as the tensile strength. For certain applications a multifilament
structure is preferred. In either case the suture material is then passed
through an iodine bath made according to the recipe given earlier. The
residence time in the bath may be from a few seconds to a few minutes
depending upon the amount of iodine desired in the complex. The material
is then washed in water and air dried.
For bandage applications a suitable fabric is woven or knitted from nylon-4
textile fiber and treated in the iodine bath in a similar manner.
EXAMPLE
A sample of 100% nylon-4 knit tubing weighing 11.0 grams was immersed in a
11/2% iodine solution prepared as follows:
6.0 grams elemental iodine
12.0 grams of potassium iodide
400 ml water.
After 5 minutes the fabric was removed, rinsed four times with cold water
and then air dried. The dried fabric was chocolate brown in color.
The fabric was tested for microbiological activities by an independent
laboratory using a modified Kirby-Bauer Susceptibility Disk Diffusion
Test. The only modification to the standard procedure was that the fabric
was cut into squares approximately 1.5 centimeters on a side instead of
the routinely used antibiotic assay discs.
The following four strains of bacteria were separately grown in
Trypticase-soy broth at 35.degree. C. until a density of 0.5 MacFarland
turbidity was observed (approximately 5.times.10.sup.7 organisms per
milliliter): Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus
mirabilis and Staphylococcus aureus. Using a sterile cotton swab, a lawn
of each bacterial isolate was applied to individual 150 mm plates of
Mueller-Hinton agar. Three squares of test fabric were placed on the agar
surface of each plate. The plates were incubated at 35.degree. C. for 18
hours.
The average zones of inhibition of bacterial growth as measured in
millimeters from the edge of the fabric to the point of uninhibited
bacterial growth were as follows:
______________________________________
Klebsiella pneumoniae
25 mm
Pseudomonas aeruginosa
15 mm
Proteus mirabilis 12 mm
Staphylococcus aureus
30 mm
______________________________________
The zones of inhibition are due to the diffusion of iodine from the complex
into the agar rather than to the release of iodine vapor above the plate.
The difference in the zones of inhibition reflects the differential
sensitivity of the organisms to the iodine rather than differences in
diffusion rates.
The nylon-4 iodine complex may be utilized in many other ways, for example
as an inner layer in packaging to serve as a biocidal barrier thus keeping
the contents of the package sterile, or as a source of a low concentration
of iodine vapor to provide a sterile atmosphere. Since there are many
different embodiments of this invention which may be made without
departing from the spirit and scope thereof, it is to be understood that
the invention is not to be limited by the above examples except as defined
in the appended claims.
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